Burnham Institute Touches Down in Orlando

BY NICK ZAGORSKI

In 1963, Walter Elias Disney flew over an uninhabited stretch of swampland near Orlando, Fla., and saw a vision of the future: a completely new type of theme park that would dwarf even his revolutionary Disneyland in Anaheim, Calif. Occupying more than 20,000 acres, this new amusement park in the center of the Sunshine State would be large enough to contain all the necessities of a family vacation— attractions, dining, shopping, leisure— and also grow and change over the years.

A side view of the Burnham Institute at Lake Nona building, which officially opened with a dedication ceremony on Oct. 8; the front portion of the building (left) houses the administrative wing, while the labs and technology centers are in the back (right)

Although Disney did not live to see the opening of his “Florida Project,” his dream definitely has been realized, for those once-empty parcels of land now contain one of the most-visited destinations in the world— a grand resort that helped transform the theme park and tourism industries.

Thirty-six years later, another successful California enterprise has come to Orlando, as this past October La Jolla’s Burnham Institute for Medical Research has opened up a brand new $85 million research facility. Burnham’s new building may not be quite as eye-catching as Spaceship Earth at Epcot, and it probably won’t bring in quite as many tourists as its illustrious neighbor; however, the expansion of this private biomedical research institute into Orlando, along with the other planned research and medical facilities that eventually will make up a biotechnology park, has just as much potential to be extraordinarily transformative to the state of Florida as Walt Disney World.

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Traditionally, Florida’s economy has been supported by three primary industries: tourism, agriculture and construction. All of those, though, are sensitive to factors beyond the state’s control, such as unpredictable weather and global economic factors. And, much like any three-legged object, kicking out even one leg destabilizes the whole thing.

Back in 2003, then-Florida Gov. Jeb Bush began looking for a fourth leg to provide more long-term economic growth and stability and saw an opportunity in biotechnology.

Somewhat surprisingly, despite having the fourth-largest state population, four major metropolitan areas and several large universities and hospitals, Florida never has been a major player in biotech. Burnham associate professor Masanobu Komatsu, who completed his undergraduate, graduate and first postdoctoral work at the University of Miami, saw that firsthand. “I really liked the area. It’s where I met my wife, and I didn’t want to leave, but at that time Florida didn’t offer much of a career future in cancer research.”

Bush hoped to change such perceptions, and he drew inspiration from another sunny, tourist-driven location: San Diego, which gradually had built up a vibrant biotechnology industry, basically starting from scratch. It most certainly would be a risky proposal, but it would be one with high reward potential. A successful biotech cluster would create thousands of jobs, generate tremendous revenue and increase Florida’s intellectual capital. So, the state began wooing the best in biotech to its sunny shores.

And, although the Burnham Institute for Medical Research was not the first to set foot in Florida— that honor actually would go to its neighbor in La Jolla, the Scripps Research Institute— its arrival is part of Florida’s most ambitious recruiting effort to date. While other biotechnology hubs like San Diego and Boston took decades to fully develop, Orlando hopes to jump-start the biotech boom by quickly attracting multiple established institutes, as opposed to untested startups, to a ready-to-develop 600-acre site in southeastern Orlando near Lake Nona known as “Medical City.”

And the cornerstone of this city would be the Burnham Institute for Medical Research.

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From its origins as a research center aimed at understanding the development of cancer, Burnham has built up a scientific mission of tackling disease via fundamental discovery and innovative technology, whether through its continued work as a National Cancer Institute-designated cancer center, or other areas, such as infectious and inflammatory disease, neuroscience and stem-cell research.

That disease-driven mission will continue to be represented in Orlando, although, like any sibling, this site also will find its own identity by pursuing an avenue of research that is complementary to research at the La Jolla institute: understanding metabolism and how it relates to obesity, diabetes and cardiovascular disease. “This new center is thematically distinct, which gives us a reason to be,” explains Burnham at Lake Nona scientific director Daniel P. Kelly, “but our studies also extensively cross-cut with Burnham’s other themes, which lets the two campuses stay connected.”

The Lake Nona institute will be headlined by the Diabetes and Obesity Research Center, which is composed of two distinct programs: the metabolic signaling and disease program and the cardiovascular pathobiology program. In turn, the research carried out by those two programs will be supported by several advanced technology platforms, such as high-throughput small-molecule screening, genomics, metabolomics, medicinal chemistry and pharmacology. Some of the technologies, like medicinal chemistry, are extensions of platforms that Burnham has in La Jolla, while others, like genomics, were developed to complement Lake Nona’s research areas. Two platforms, though, were developed specifically to give this new center a unique feel.

The first technology is a very extensive small-animal phenotyping core that will allow researchers to evaluate insulin resistance, body fat mass and composition, heart function and energy expenditure of mouse models. The second is a metabolomics platform, set up in collaboration with Duke University’s Sarah W. Stedman Nutrition and Metabolism Center, which will conduct mass-spectrometry-based metabolite profiling.

“Both of these sophisticated technology resources can put into overdrive our opportunity to do translational research that could not be done at traditional academic institutes,” says Kelly, who was at Washington University School of Medicine in St. Louis prior to taking the scientific director role in early 2008.

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“An Out-of-the-Box Proposal.” That curiously titled e-mail header, from Kelly, was Philip A. Wood’s first introduction to Burnham’s Orlando facility. “I had known Dan for about 20 years,” says Wood, who was a professor at the University of Alabama at Birmingham when that message hit his inbox last year. “We had published some papers together and gave talks on the same stages, so I decided to give it a look. After all, an out-of-the-box proposal was exactly what I needed at that point in my career.”

A leading expert in animal models of disease, Philip A. Wood came to Burnham at Lake Nona to unravel the genetics behind rare inherited metabolic diseases as well as complex traits like metabolic syndrome.

After a visit to Orlando that he describes as completely first class, Wood was hooked. “Everything was just so well done and efficient; all the resources I wanted for my studies into fatty acid oxidation and how the body handles increased fat loads— metabolic physiology, genomics and metabolomics— were under one roof, and I realized I could do my research here with minimum aggravation. Add in the fact that I don’t really like snow, and coming here was a no-brainer.”

From Kelly’s point of view, bringing Wood on board was also an easy decision. As a trained veterinarian with more than 30 years of experience, Wood knew the medicine and genetics of seven different species, which allowed him to think in comparative terms. That kind of broad expertise was perfect for Kelly’s vision of assembling a diverse research team that could take advantage of the technology platforms.

“I was very keen on developing an environment without barriers,” says Kelly. “Looking at it from a discovery sense, we need to consider metabolism from many different disciplines.”

That meant bringing in scientists with Ph.D.s, M.D.s and even D.V.M.s, as well as mixing strong academics like Timothy Osborne, who was a professor of biochemistry and molecular biology at the University of California, Irvine, before coming over as metabolic signaling and disease program director, with industry types like Stephen Gardell, who had spent 20 years working in drug discovery at major pharmaceutical companies.

The pace of hiring has been extremely rapid, with 14 of an anticipated 30 lead scientist positions already filled since Burnham first agreed to expand to Orlando back in August 2006. Kelly attributes that pace partially to luck, partially to Burnham’s existing reputation and partially to his nature. “I don’t want a sparsely populated building, you know, because the technology cores need collaborators to get up and running,” he says. “So I’ve been hard on the recruitment trail.”

The location certainly helps as well: “I grew up in Wisconsin and was always a Midwest guy, so Florida was always the least likely area I thought I would live in,” Kelly says. But he adds that for others, such as empty-nesters or people with children, Florida has a sort of magnetic appeal.

Osborne is a prime example. Tenured and quite content at Irvine, he initially came to visit with his wife out of curiosity and professional courtesy, but he was quickly won over. “Everyone we met, none of whom knew us from Adam, was amazingly friendly and treated us so well, and the facilities were amazing,” he says. “To put it simply, we were just floored.”

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While Burnham received a generous start-up package from state, local, and private groups, Kelly acknowledges that, in the long term, Burnham at Lake Nona cannot be sustainable purely on the National Institutes of Health funding received by its scientists.

The University of Central Florida’s brand new medical school is just one of several buildings set to join Burnham in Medical City.

For its continued success, and the success of Florida biotech, it’ll need philanthropy and business interests, and therefore productive partnerships with universities, hospitals and companies. Fortunately, buoyed by Burnham’s early commitment, Medical City will provide many partnership opportunities; already, the University of Central Florida is nearing completion of its brand new medical school just down the road from Burnham, while Nemours Children’s Hospital, the M.D. Anderson Cancer Center Orlando and the University of Florida also have agreed to build facilities there.

But while the presence of a life science cluster at Lake Nona will be extremely beneficial, Burnham also has undertaken a forward-looking model to ensure its research effort is maximized.

That’s where Gardell comes in. In his specialized role as director of translational research resources, he oversees Burnham’s two flagship high-technology platforms— metabolomics and cardiometabolic phenotyping— and assists researchers in shepherding their projects toward clinical utility, which in turn, he believes, will further Burnham’s mission. “Translational research is a circular process,” he says. “It involves bench-to-bedside— and bedside-to-bench research pursuits. Discoveries made in the clinics must feed back to guide basic research. This is a critical component of overall success.”

Burnham Institute researchers Steven R. Smith (left), director of the Florida Hospital-Burnham Institute Translational Research Institute, and Stephen Gardell, director of Burnham’s translational research resources, both will be instrumental in fulfilling the institute’s aims of pushing its fundamental discoveries toward clinical and industrial utility.

Speaking of bedsides, Gardell will work closely with Steven R. Smith, a trained endocrinologist who was hired by Burnham in a joint appointment with Florida Hospital. When he’s not in lab studying genetic and epigenetic changes that may alter muscle metabolism, Smith heads the Florida Hospital-Burnham Institute Translational Research Institute. The TRI, which will also soon have its own state-of-the-art building, employs clinical scientists conducting patient-oriented research who will work closely with Burnham to apply their work back to basic research. Smith envisions that, just like him, some other TRI researchers will have joint labs at Burnham, thus making the collaboration even more intertwined.

Such collaboration will be essential because, in choosing diabetes and obesity as its research focus, Burnham at Lake Nona has taken up quite a challenge. As Smith discusses his clinical work, he points to a graph of obesity trends, and the hockey-stick like rise seen over the past decade. Diabetes rates have not yet advanced that high, but Smith notes somberly, “Diabetes usually follows obesity by about 10 years.”

And diabetes is no simple beast: “You can find as many theories about the mechanisms underlying insulin resistance as you have labs working on it,” Wood says, adding, “Just look at cholesterol problems by comparison, where statin drugs are highly effective. We have no statin equivalent in diabetes; after all these years, the best treatment is still diet and exercise.”

If anyone’s up to the challenge of changing that, it may be the Burnham. “We’ve got a great institute that’s focused on a core set of principles, where everyone loves to get together and talk about ideas,” Smith says. “I’m optimistic we’ll get some good things done.”